Walking the path to leadership in cancer immunotherapy: Dr Sean Lim, Advanced Clinician Scientist Fellow

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Advanced Clinician Scientist Fellowship (ACSF) holder Dr Sean Lim is Associate Professor and Honorary Consultant in Haematological Oncology at the University of Southampton and University Hospital Southampton NHS Trust, leading her own research group.

Sean is at the ‘Establish independence’ stage in our Competency Framework for Fellowships. Here, she explains how she has built on her previous Clinician Scientist Fellowship (CSF) and demonstrated in her application the skills and experience we expect of researchers at this point in their careers. She also tells us how our ACSF is enabling her to develop agnostic immunotherapy approaches to modulate the cancer immune response and improve treatment of B-cell lymphoma.

Career stage: establishing independence

I applied for the ACSF towards the end of my CSF. During the CSF, I’d spent two years in a world-class immunotherapy lab at Stanford, led by Professor Ron Levy. I used this experience to differentiate myself from my local peers and supervisors and develop my own niche. The ACSF was the perfect fit because it allowed me to continue practicing medicine and use that clinical experience to shape my research ideas. I was able to have dedicated research time to build my group. There aren’t that many funding bodies that enable you to combine these things, so it seemed obvious that I would try to continue my funding with Cancer Research UK (CRUK). 

Research experience: driving translation and gaining recognition

During my CSF I demonstrated that immunostimulatory monoclonal antibodies, beyond their known effects on T-cells, indirectly activate cells associated with the innate immune system. I translated this finding in an early-phase clinical trial funded by CRUK in which two existing immunotherapy drugs, varlilumab and rituximab, are combined to treat B-cell lymphoma. I am Chief Investigator on this trial, had secured additional funding from Cancer Research UK and other sources, and had written several senior-author publications—which helped to show that I had conceptualised and driven a project—when I applied for the ACSF.  

The CSF also enabled me to expand my collaborative network and I started to receive invitations from international organisations to speak at conferences and meetings. It was a real honour when I received an invitation to act as an expert reviewer for one of the National Institute for Health and Care Excellence (NICE) technology appraisals for an antibody therapy in lymphoma.  

Future research ambitions:  producing new insights into immunotherapy mechanisms

One of the big unknowns in cancer immunotherapy is why only some people respond to treatment. The lack of adequate agonistic antibodies to further boost anti-tumour immunity and increase response rates and overall survival is also problematic. It is critical that we understand the mechanisms and rules underlying the activity of effective immunotherapies. My ambition is to further our understanding of the innate and adaptive immune interface and to use antibody therapy to develop effective long-term treatment. I hope to do this by developing an excellent research programme that is driven by what I see in the clinic. Being a clinician scientist certainly helps with asking a scientific question that has translational potential.    

Skills: gaining good management and communication skills

There’s a lot of learning on the job and following in the footsteps of your local mentors and leaders. I was fortunate to have many extremely supportive local mentors, as well as one from the CRUK Women of Influence Initiative, a mentoring scheme that pairs CRUK fellows with leading business women outside of academia. 

I realised that to drive the development of my own independent research group I needed to gain good management and supervisory skills. My role as a consultant gave me some experience in team management and during my CSF I managed a technician and supervised a PhD student. To supplement this, I attended a PhD supervisors’ course and completed appraisal development training. I also undertook a course on how to be a chief investigator of a clinical trial, as this was an entirely new experience for me.

I have always actively tried to disseminate my research to the public. CRUK is funded by the public’s generosity so it’s our responsibility to communicate our research. I‘ve hosted lab tours, spoken at fundraising events and taken part in media campaigns. I also try to explain my research on a one-on-one basis with patients. 

Looking to the future

My research is diversifying. When I applied to the ACSF I had one, very defined, research programme; now, I’m branching out to different areas and applying for more funding and resources, which is all really quite exciting. Several new collaborations and a rapid increase in invitations to speak at conferences are bringing in new and fresh ideas.

Cancer immunotherapy is advancing fast and has the potential to fundamentally alter the landscape of clinical practice. This area is now about actualising the science and improving antibody-based treatments for cancer patients. To do that successfully, I want to practice excellent science, disseminate my findings, and get more grants to support this work. My long-term aim is to be identified as a leader in the field of cancer immunotherapy.